Quantitative characterization of tissue structure and function is one of the most challenging problems in Medical Imaging. Field of view, depth of interrogation, and resolution are critical features that dramatically impact image quality and information content. To this end, we propose to further the development of a device that exploits a new imaging technique known as Modulated Imaging (MI) and to benchmark the sensitivity of this device to provide objective parameters that can be used to determine status of in-vivo tissue, enabling quantitative insight into disease progression and therapeutic response. We believe the value of this technology will be particularly strong in its application toward acute an chronic wound assessment. Modulated Imaging employs patterned illumination to non-invasively obtain subsurface images of biological tissues. Recently developed under the Laser and Medical Microbeam Program (LAMMP), an NIH/NIBIB P41 Biomedical Technology Resource Center, this non-contact approach enables rapid, quantitative determination of the optical properties of tissues over a wide field-of-view. When combined with multi-spectral imaging, MI can be used to quantitatively determine the in-vivo concentrations of chromophores that are relevant to tissue health, namely, oxy- and deoxy-hemoglobin and water. Modulated Imaging can be executed using consumer grade electronics such as those currently employed in digital cameras and DLP projectors. Hence, it is plausible to consider the potential for Modulated Imaging to be executed as a relatively inexpensive medical device. The broad goal of this proposal is to develop a robust, user-friendly MI platform capable of quantitative imaging over a wide-field (25 x 34 cm) and appropriate for deployment at clinical sites. It will possess sufficient spatio-temporal resolution to study both fast (i.e., <1s timescale) and localized (i.e.,<1 mm) events at depths of several millimeters in thick tissues, with application areas such as chronic wound healing, pressure sore staging, burn assessment, and reconstructive surgery. To achieve this, we will design and deploy to clinical collaborators a final MI system platform enabling turn-key clinical research. The proposed research will include the following steps: 1) Design and fabricate a clinic-ready Modulated Imaging hardware platform with increased field-of-view, spectral multiplexing, improved stability and enhanced ease of use, 2) Develop clinic-friendly software with automated analysis and refined algorithms, 3) Develop and perform internal and external validation and verification processes and procedures and 4) Conduct in-vivo evaluations to establish benchmarks of performance and sensitivity for quantitative hemoglobin and water parameter recovery. Upon successful completion of the Phase II research outlined herein, we intend to rigorously pursue Phase III clinical studies, 510(k) device clearance and ultimate commercialization of our final OxImager product.